mRNA expression profile of bronchoalveolar lavage fluid cells from patients with idiopathic pulmonary fibrosis and sarcoidosis

Eur J Clin Invest. 2019 Sep;49(9):e13153. doi: 10.1111/eci.13153. Epub 2019 Jul 11.

Abstract

Background: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the fibrotic changes in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular analysis of BALf cells from IPF and sarcoidosis patients.

Methods: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real-time PCR in 32 samples (11 IPF and 21 sarcoidosis).

Results: The number of genes differentially expressed between IPF and sarcoidosis groups was 4832 (13359 probesets). Cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis.

Conclusions: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells. The most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.

Keywords: bronchoalveolar lavage fluid; idiopathic pulmonary fibrosis; interstitial lung diseases; mRNA; sarcoidosis.

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Lymphocytes
  • Male
  • Matrix Metalloproteinases / genetics
  • Middle Aged
  • Neutrophils
  • Organelle Biogenesis
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Ribosomes
  • Sarcoidosis, Pulmonary / genetics*
  • Transcriptome
  • Up-Regulation

Substances

  • RNA, Messenger
  • Matrix Metalloproteinases